Non-insulin dependent diabetes mellitus (NIDDM) is associated with deranged insulin secretion. When an increased insulin output is required due to peripheral resistance to insulin, the 6-cells of the pancreas no longer respond adequately. We are studying factors that lead to defective secretion and to the increased peripheral resistance. It had been shown that the constitutive nitric oxide synthase is present in beta cells of the pancreas. Therefore, a possibility arose that nitric oxide might be required for adequate glucose-mediated insulin release. However, using a competitive inhibitor to nitric oxide synthase in the presence of various glucose concentrations, we failed to detect an effect on insulin release. In the process of evaluating nitric oxide as a potential second messenger in fat cells, we failed to detect nitric oxide synthase. However, we did find that amino acids, specifically arginine and glutamate, increased glycogen synthesis in response to insulin. We plan to investigate this further and ascertain if this modulation of glycogen synthesis by amino acids might be affected in NIDDM.